Crystal structure of glycinamide ribonucleotide transformylase from Escherichia coli at 3.0 A resolution. A target enzyme for chemotherapy

J Mol Biol. 1992 Sep 5;227(1):283-92. doi: 10.1016/0022-2836(92)90698-j.


The atomic structure of glycinamide ribonucleotide transformylase, an essential enzyme in purine biosynthesis, has been determined at 3.0 A resolution. The last three C-terminal residues and a sequence stretch of 18 residues (residues 113 to 130) are not visible in the electron density map. The enzyme forms a dimer in the crystal structure. Each monomer is divided into two domains, which are connected by a central mainly parallel seven-stranded beta-sheet. The N-terminal domain contains a Rossmann type mononucleotide fold with a phosphate ion bound to the C-terminal end of the first beta-strand. A long narrow cleft stretches from the phosphate to a conserved aspartic acid, Asp144, which has been suggested as an active-site residue. The cleft is lined by a cluster of residues, which are conserved between bacterial, yeast, avian and human enzymes, and likely represents the binding pocket and active site of the enzyme. GAR Tfase binds a reduced folate cofactor and glycinamide ribonucleotide for the catalysis of one of the initial steps in purine biosynthesis. Folate analogs and multi-substrate inhibitors of the enzyme have antineoplastic effects and the structure determination of the unliganded enzyme and enzyme-inhibitor complexes will aid the development of anti-cancer drugs.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyltransferases / ultrastructure*
  • Crystallography
  • Escherichia coli / enzymology
  • Hydroxymethyl and Formyl Transferases*
  • Models, Molecular
  • Phosphates
  • Phosphoribosylglycinamide Formyltransferase
  • Protein Conformation
  • Temperature
  • X-Ray Diffraction


  • Phosphates
  • Hydroxymethyl and Formyl Transferases
  • Phosphoribosylglycinamide Formyltransferase
  • Acyltransferases